Search PubMed⌕ Search

Biomedical subjects

G A Kuchel

Publications and source records attributed to G A Kuchel.

13 recordsLinked to original sources
PubMed1997

Decreased neurofilament gene expression is an index of selective axonal hypotrophy in ageing.

Axonal atrophy may reflect earlier and more reversible events in neurodegeneration and ageing than somatic atrophy. Innervation density by sympathetic fibres from the rat superior cervical ganglion (SCG) to the middle cerebral artery (MCA) decreases dramatically in old age, while that to the iris is largely unchanged. In situ hybridization was used in conjunction with retrograde tracers to examine the role of the neuronal cytoskeleton in this selective axonal vulnerability. Using a riboprobe complementary to neurofilament light chain (NF-L) mRNA, there was a 22-25% decrease in the mean grain density in aged neurones when all neurones were examined. A small subset of these neurones was shown to project to the MCA and another to the iris. In young SCG, both subpopulations expressed intermediate grain densities for NF-L mRNA. In MCA-projecting neurones, there was a 40% decline in grain density with ageing (p < 0.05), with no change in iris-projecting neurones. Our results demonstrate that major decreases in NF-L expression may represent cellular markers of selective axonal hypotrophy by aged neurones.

Aging↗
PubMed1996

Decreased neurofilament gene expression is an index of selective axonal hypotrophy in ageing.

Axonal atrophy may reflect earlier and more reversible events in neurodegeneration and ageing than somatic atrophy. Innervation density by sympathetic fibres from the rat superior cervical ganglion (SCG) to the middle cerebral artery (MCA) decreases dramatically in old age, while that to the iris is largely unchanged. In situ hybridization was used in conjunction with retrograde tracers to examine the role of the neuronal cytoskeleton in this selective axonal vulnerability. Using a riboprobe complementary to neurofilament light chain (NF-L) mRNA, there was a 22-25% decrease in the mean grain density in aged neurones when all neurones were examined. A small subset of these neurones was shown to project to the MCA and another to the iris. In young SCG, both subpopulations expressed intermediate grain densities for NF-L mRNA. In MCA-projecting neurones, there was a 40% decline in grain density with ageing (p < 0.05), with no change in iris-projecting neurones. Our results demonstrate that major decreases in NF-L expression may represent cellular markers of selective axonal hypotrophy by aged neurones.

Aging↗
PubMed1993

Alterations in target innervation and collateral sprouting in the aging sympathetic nervous system.

The ability to sustain appropriate target innervation and to undergo collateral sprouting following losses of related neural inputs may favor the maintenance of normal function in adult and aged organisms. Young (4 month old) rats underwent a unilateral sympathetic denervation of the pineal gland and 1 day later exhibited an approximately 50% decrease in the area fraction represented by tyrosine hydroxylase (TH)-immunoreactive profiles in this target tissue. Ten days after this lesion, the density of TH immunoreactivity increased to over 80% of control values. In aged (25 month old) animals, endogenous fluorescence produced by the presence of lipofuscin was subtracted from the captured image, revealing a more than 50% decrease in innervation density to this target tissue with aging. The density of TH-immunoreactive profiles decreased by approximately one-half in aged animals lesioned 1 day earlier. However, 10 days after a unilateral denervation it was still approximately one-half of that obtained in control aged rats, providing morphologic support for a failure in collateral sprouting with aging in this system.

Aging↗
PubMed1993

Decline in response to nicotine in aged rat striatum: correlation with a decrease in a subpopulation of nicotinic receptors.

Specific and reproducible changes involving the cholinergic and dopaminergic systems have been described in both the aging rodent and the human nervous system. Nevertheless, relatively little information is available on changes in nicotinic cholinergic receptors occurring in normal aging, and there have been few attempts to correlate alterations in receptor densities with changes in nicotinic actions. We have utilized the nicotine-mediated stimulation of endogenous dopamine efflux in a striatal slice preparation as a functional index of responsiveness to nicotine in aging. Following incubation with nicotine, this efflux was significantly lower in 25-month-old (aged) as opposed to 4-month-old (young) rats. In contrast, the release of striatal dopamine following a high-potassium stimulus was similar at both ages. Binding studies in young and aged animals did not reveal any significant change with age in the total number of striatal nicotinic receptors recognized by either [3H]nicotine or the neuronal nicotinic antagonist 125I-neuronal bungarotoxin. However, there was a nearly 80% decline in the subpopulation of striatal nicotinic receptors jointly recognized by both nicotine and neuronal bungarotoxin, but not by alpha-bungarotoxin. Quantitative autoradiography demonstrated declines with age in this receptor subtype in several brain regions examined. Decrements in this specific subpopulation of nicotinic receptors or in the nerve cells expressing these receptors may contribute to the functional declines that take place in the aging motor and visual systems.

Aging↗
PubMed1992

Transynaptic regulation of low-affinity p75 nerve growth factor receptor mRNA precedes and accompanies lesion-induced collateral neuronal sprouting.

The bilateral sympathetic innervation of the rat pineal gland from the two superior cervical ganglia (SCG) is a useful model system to investigate the mechanisms by which intact neurons compensate for neuronal losses. Cutting of the internal carotid nerve (ICN) on one side has been shown to result in the removal of approximately one-half of the innervation to the pineal gland within 2 days. This denervation is followed by the development of collateral neuronal sprouting from the contralateral "intact" SCG, most of which takes place during the next 2 days. Using a solution hybridization protection assay, levels of low-affinity NGF receptor p75NGFR mRNA (pg/microgram total RNA) were found to be increased 25%, with no change in cyclophilin mRNA, in the SCG contralateral to the lesion performed 1 or 3 days earlier. In situ hybridization with a 35S riboprobe complementary to p75NGFR mRNA demonstrated a large increase in this mRNA in some cells of this intact SCG at both 1 and 3 days after a contralateral ICN cut lesion. The clustering of these cells toward the rostral portion of the SCG suggests that they may overlap with the population of sympathetic neurons which provides innervation to bilaterally innervated structures such as the pineal gland. The nature of the signals involved in the regulation of NGF receptor mRNA levels and their role in initiating and maintaining collateral sprouting remain to be fully established. Nevertheless, the time course of the changes in mRNA levels suggests that regulation of the low-affinity NGF receptor gene may be involved in the sequence of events associated with the collateral sprouting response by intact sympathetic nerve cells following partial denervation.

Amino Acid Isomerases↗
PubMed1992

Cardiovascular responses to phlebotomy and sitting in middle-aged and elderly subjects.

BACKGROUND: Responding appropriately to hypotensive challenges is an important determinant of health and functional independence in elderly individuals. Cardiovascular responses to phlebotomy and postural change were evaluated using a large database developed in a study designed to establish the safety of blood donation by older individuals. METHODS: The groups studied included 464 subjects aged 65 years and younger (range, 52 to 65 years) and 532 subjects more than 65 years old (range, 66 to 78 years old). Blood pressure and pulse rate measurements were followed by the withdrawal of 500 mL of blood. These measurements were repeated, first in the supine and then in the sitting position. RESULTS: Nearly all individuals studied remained hemodynamically stable after these two challenges. Age was not an independent predictor of blood pressure change after either phlebotomy or postural change. Large decreases in diastolic blood pressure were equally rare in both age groups. However, more older subjects (15.2%) exhibited a decline of 20 mm Hg or more in systolic blood pressure following phlebotomy, compared with the middle-aged group (6.9%). These age-related differences did not persist after controlling for the higher initial systolic blood pressures observed in the older subjects. Postphlebotomy postural change to the sitting position had little additional effect. CONCLUSIONS: These results indicate that the ability to respond to hypovolemia and postural change remains relatively intact in healthy elderly individuals. The higher prevalence of a significant drop in systolic blood pressure after phlebotomy, orthostasis, and possibly other homeostatic challenges in older subjects is probably due to the presence of higher basal blood pressure readings, including hypertension. In spite of these differences, blood donation is appropriate and should be encouraged in healthy elderly individuals in this age group.

Aged↗
PubMed1991

Functional recovery and collateral neuronal sprouting examined in young and aged rats following a partial neural lesion.

The rat pineal gland was chosen as a model system to study how aging affects the capacity of surviving neurons to compensate for partial destruction of a neural pathway. The pineal gland receives bilateral overlapping sympathetic innervation from the two internal carotid nerves, whose activity regulates several aspects of pineal metabolism in a circadian fashion. The most dramatic of these is the marked nighttime increase in the activity of N-acetyltransferase, the rate-limiting enzyme in melatonin synthesis. These features allow for the pineal gland to be used as a model system for studies on neuronal plasticity, since it is possible to create specific partial neural lesions and to evaluate functional recovery subsequently at the cellular level. We examined the activity of N-acetyltransferase and the content of melatonin in the pineal gland as indices of pineal function at various time points after unilateral surgical denervation (lesion of one of the two internal carotid nerves) in 4-month-(young) and 25-month-old (aged) rats. At both ages, the nighttime levels of the two parameters were significantly lower 8 h after this lesion than in sham-operated animals of the same age, indicating impaired function. When examined at later time points (i.e., 1.5 and 10 days after this lesion), both young and aged animals exhibited full recovery in these two parameters. Measurement of specific neuronal uptake of [3H]norepinephrine was utilized as an index of the number of sympathetic varicosities innervating the pineal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Peripheral dopamine in pathophysiology of hypertension. Interaction with aging and lifestyle.

Dopamine, an ancestral catecholamine, is physiologically natriuretic and vasodilating, thus essentially protecting against hypertension. Its actions are overshadowed by the opposite effects of its main biological partner, norepinephrine, and this is accentuated with aging. Clinical observations combined with molecular biology approaches to catecholamine-synthesizing and catecholamine-metabolizing enzymes and receptors permit the identification of some inborn defects. Subtle changes in the dopamine-norepinephrine balance may account for the enhanced peripheral noradrenergic activity seen in the setting of decreased dopaminergic activity in advanced age. These changes may contribute to the diminished ability of the aged kidney to excrete a salt load, as well as to the finding that systolic blood pressure increases with age in populations with a high, but not in those with a low, intake of salt. The attainment of advanced age in Western societies with adverse lifestyle changes (mental rather than physical stress, excess salt intake, overeating, sedentarism) appears to facilitate the development of hypertension. The adaptation to all the preceding lifestyle changes necessitates an increased dopamine generation, which may initially compensate to maintain appropriate natriuresis and vasodilation since many patients with initial borderline essential hypertension express their sympathetic hyperfunction, in addition to increased norepinephrine release, by excessive dopamine release. However, the progression of hypertension is accompanied by a peripheral dopaminergic deficiency and diminished ability to excrete salt. This may represent an eventual inadequacy of a phylogenetically redundant system resulting in decreased natriuresis and vasodilation and may account for the responsiveness of established chronic hypertension to salt restriction, diuretics, and dopaminomimetic medication.

Aging↗
PubMed1990

Recovery of function following unilateral denervation, but not unilateral decentralization, of the pineal gland as indicated by measurements of pineal melatonin content and urinary melatonin metabolites.

The rat pineal gland is an attractive system for studies on the capacity of neural systems to recover following partial injury, allowing both for the creation of precise subtotal lesions and for the measurement of recovery of function at the cellular level. The pineal gland receives overlapping sympathetic innervation from the right and left internal carotid nerves from neurons whose cell bodies are located in the two superior cervical ganglia. This innervation regulates several aspects of pineal metabolism in a circadian fashion, with the most dramatic being a marked increase in the night-time activity of N-acetyltransferase, a key enzyme regulating the rate of melatonin synthesis. We have previously shown that a highly divergent pattern takes place in the night-time activity of this enzyme following two different unilateral lesions of the sympathetic innervation to the gland. Thus, following a unilateral lesion of the internal carotid nerve (unilateral denervation), there is an initial decline in N-acetyltransferase activity; however, normal activity is again seen during the second and subsequent nights. In contrast, a unilateral lesion of the cervical sympathetic trunk, the nerve that innervates the superior cervical ganglion (unilateral decentralization), results in "permanent" impairment of N-acetyltransferase activity. In the present study, we report that the functional capacity of the entire pathway for melatonin synthesis is similarly affected following these lesions, as reflected by the levels of melatonin and of its precursor N-acetylserotonin in the pineal gland, as well as the levels of the main melatonin metabolite 6-hydroxy-melatonin in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Neurotrophin receptor and tyrosine hydroxylase gene expression in aged sympathetic neurons.

Ribonuclease protection measurements revealed decreases of 26% in p75 neurotrophin receptor mRNA and 30% in trkA mRNA in superior cervical ganglia (SCG) of aged Long-Evans rats. These declines were not related to the presence of a spatial memory impairment, whose presence is known to strongly predict increased hypothalamic-pituitary-adrenal axis activity in these aged animals. A similar decrease with age was observed in p75, but not cyclophilin mRNA levels in SCG from F-344 inbred rats. In situ hybridization with paired sections from mature and aged F-344 rats revealed a 25% decline in the mean neuronal labeling index (LI) for p75 mRNA. In other paired sections, mean trkA LI decreased 16%, tyrosine hydroxylase (TH) LI increased 74% and cyclophilin LI did not change. Neuronal hypertrophy, p75 decreases and TH increases all occurred to a greatest extent in intermediate-sized neurons, resembling those innervating the pineal and cerebral vessels. In contrast to other SCG targets, this innervation is known to decline nearly 50% with aging. Retrograde tracer/in situ hybridization studies will be required to establish whether decreased p75 represents a marker for selective axonal regression and also to determine the significance of increased TH and neuronal hypertrophy.

Adrenocorticotropic Hormone↗